ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.3277C>T (p.Arg1093Cys)

gnomAD frequency: 0.00002  dbSNP: rs72656307
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631466 SCV000752546 uncertain significance Osteogenesis imperfecta type I 2023-07-04 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects COL1A1 function (PMID: 17211858). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL1A1 protein function. ClinVar contains an entry for this variant (Variation ID: 161457). This missense change has been observed in individual(s) with multiple arterial dissections and osteopenia with wrist fractures (PMID: 17211858). This variant is present in population databases (rs72656307, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1093 of the COL1A1 protein (p.Arg1093Cys).
GeneDx RCV001753528 SCV001986032 uncertain significance not provided 2020-07-14 criteria provided, single submitter clinical testing Has been reported in an individual with aortic dissection and aneurysms, but without other features of EDS (Malfait et al., 2007); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Located in the Gly-Xaa-Yaa triple helical region of the pro-alpha1(I) chain encoded by the COL1A1 gene, where triplet glycine substitutions are the most common cause of osteogenesis imperfecta (OI). The effect of missense substitution at the X and Y positions are more difficult to predict; however, multiple variants that result in introduction of a Cys residue in pro-alpha1(I) have been reported to be pathogenic (Dalgleish, 1998).; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 161457; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 17211858, 28306225)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277297 SCV002565516 uncertain significance Ehlers-Danlos syndrome 2018-10-01 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002288660 SCV002580206 uncertain significance Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 2021-09-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002492548 SCV002783739 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I; Osteoporosis; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 2022-01-14 criteria provided, single submitter clinical testing
Science for Life laboratory, Karolinska Institutet RCV000148991 SCV000088633 unknown Malignant tumor of prostate no assertion criteria provided not provided Converted during submission to Uncertain significance.

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